Universität zu Köln

Engelhardt, Pascal M., Florez-Rueda, Sebastian, Drexelius, Marco, Neudoerfl, Joerg-Martin, Lauster, Daniel, Hackenberger, Christian P. R., Kuehne, Ronald, Neundorf, Ines and Schmalz, Hans-Guenther ORCID: 0000-0003-0489-1827 (2022). Synthetic alpha-Helical Peptides as Potential Inhibitors of the ACE2 SARS-CoV-2 Interaction. ChemBioChem, 23 (17). WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1439-7633

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Abstract

During viral cell entry, the spike protein of SARS-CoV-2 binds to the alpha 1-helix motif of human angiotensin-converting enzyme 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce alpha-helicity in short peptide sequences inspired by the ACE2 alpha 1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of alpha 1, a series of peptides, N-capped with either Ac-beta HAsp-[ProM-5] or Ac-beta HAsp-PP, were prepared and their alpha-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the alpha-helical content and, noteworthy, led to the identification of an Ac-beta HAsp-PP-capped peptide displaying a very strong binding affinity (K-D=62 nM).

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Engelhardt, Pascal M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Florez-Rueda, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Drexelius, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Neudoerfl, Joerg-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lauster, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Hackenberger, Christian P. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehne, Ronald UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, Hans-Guenther UNSPECIFIED orcid.org/0000-0003-0489-1827 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-672804
DOI:	10.1002/cbic.202200372
Journal or Publication Title:	ChemBioChem
Volume:	23
Number:	17
Date:	2022
Publisher:	WILEY-V C H VERLAG GMBH
Place of Publication:	WEINHEIM
ISSN:	1439-7633
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALANINE; STABILIZATION; NMR Multiple languages Biochemistry & Molecular Biology; Chemistry, Medicinal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67280